Search Results (623)

Background: Fixed-dose combinations of rosuvastatin and ezetimibe are increasingly used in clinical practice, but real-world data on their effectiveness and safety in large populations remain limited. Methods: This prospective, single-group, open-label, non-interventional observational study was conducted in the Republic of Korea to evaluate the effectiveness and safety of Rovazet^® (a fixed-dose combination of rosuvastatin and ezetimibe). Patients were prospectively enrolled from 235 institutions (50 general hospitals and 185 private clinics) as part of routine clinical practice over a five-year period. Lipid profiles and medication compliance questionnaire results were collected at baseline, 12 weeks, and 24 weeks of treatment. Results: A total of 5527 patients with dyslipidemia, the majority were men (53.0%), and the mean age was 60.4 years. Rovazet^® significantly reduced low-density lipoprotein cholesterol (LDL-C) by 23.5% at 12 weeks (from 117.47 ± 50.65 mg/dL to 81.14 ± 38.20 mg/dL; p < 0.0001) and by 27.4% at 24 weeks (from 117.47 ± 50.65 mg/dL to 74.52 ± 33.36 mg/dL; p < 0.0001). Total cholesterol was significantly reduced by 17.7% at 12 weeks and by 19.8% at 24 weeks. Rovazet^® treatment reduced triglycerides by 4.1% at 12 weeks and by 7.2% at 24 weeks. High-density lipoprotein cholesterol increased by 4.5% at 12 weeks and by 7.9% at 24 weeks following Rovazet^® treatment. These changes in lipid profiles were consistent, regardless of cardiovascular risk profiles. By 24 weeks of treatment with Rovazet^®, 91.8% of patients had reached their target LDL-C goals. Adverse drug reactions were reported in 2.81% of patients, most of which were minor, indicating that Rovazet^® was well tolerated. Conclusions: Rovazet^® was effective in improving lipid profiles and well tolerated in Korean adults with dyslipidemia. Full article

Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic, non-communicable spectrum of diseases characterized by lipid accumulation. It is often asymptomatic, and its prevalence varies by region, age, gender, and economic status. It is estimated that 25% of the world’s population currently suffer from MAFLD, and 20 million patients will die from MAFLD-related diseases. In the last 20 years, tea and anti-obesity research have indicated that regularly consuming tea decreases the risk of cardiovascular disease, stroke, obesity, diabetes, and metabolic syndrome (MeS). In this review, we aimed to present studies concerning the influence of matcha extracts and epigallocatechin-3 gallate (EGCG) supplements on metabolic functions in the context of MAFLD in human and animal studies. The published data show promise. In both human and animal studies, the beneficial effects on body weight, cholesterol levels, and liver metabolism and function were noted, even in short-period experiments. The safety levels for EGCG and green tea extract consumption are marked. More experiments are needed to confirm the results observed in animal studies and to show the mechanisms by which green tea exerts its effects. The preliminary data from research concerning microbiota or epigenetic changes observed after polyphenols and green tea consumption need to be expanded. To improve the efficiency and availability of green tea or supplement consumption as a treatment for MAFLD patients, more research with larger groups and longer study durations is needed. Full article

Deoxynojirimycin (DNJ), the first isolated iminosugar, is a natural alkaloid acting as a potent inhibitor of α-glucosidase with high nutritional value. It naturally occurs in plants (especially Morus spp.), microbes, and insects or can be synthesized. Diverse biological activities, such as antihyperglycemic, lipid-lowering, antitumor, antiviral, and anti-inflammatory, have been recognized for this compound. However, DNJ has not been approved as a food supplement until now. Several studies, also in clinics, are carried out on Morus spp. containing DNJ. Among Morus spp., Morus alba L. (white mulberry), Morus nigra L. (black mulberry), and Morus rubra L. (red mulberry) are the three main species that grow all over the world. Some spurious studies have been conducted on Reducose^® and Glubloc™, two products that contain DNJ and Morus alba, respectively. However, mulberry allergy, including respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria, may be observed. This review aims to explore a crucial and timely question: how DNJ exerts its biological effects and what role it may play in therapeutic applications. We provide a comprehensive summary of the current understanding of DNJ’s pharmacological potential and the methods used for its production. We also report recent developments in clinical studies on Morus alba, Reducose^® and Glubloc™. Full article

Copper pyrithione (CuPT), an emerging biocide used in ship antifouling coatings, may accumulate in marine sediments and pose risks to non-target organisms. However, current research on CuPT toxicity remains limited. Litopenaeus vannamei, one of the world’s most important aquaculture shrimp species, relies heavily on its hepatopancreas for energy metabolism, detoxification, and immune responses. Due to their benthic habitat, these shrimps are highly vulnerable to contamination in sediment environments. This study investigated the toxicological response in the hepatopancreas of L. vannamei exposed to CuPT (128 μg/L) for 3 and 48 h. Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) fluorescence staining revealed increased apoptosis, deformation of hepatic tubule lumens, and the loss of stellate structures in the hepatopancreas after CuPT 48 h exposure. A large number of differentially expressed genes (DEGs) were identified by transcriptomics analysis at 3 and 48 h, respectively. Most of these DEGs were related to detoxification, glucose transport, and immunity. Metabolomic analysis identified numerous significantly different metabolites (SDMs) at both 3 and 48 h post-exposure, with most SDMs associated with energy metabolism, fatty acid metabolism, and related pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of metabolomics and transcriptome revealed that both DEGs and SDMs were enriched in arachidonic acid metabolism, fatty acid biosynthesis, and glycolysis/gluconeogenesis pathways at 3 h, while at 48 h they were enriched in the starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways. These results suggested that CuPT disrupts the energy and lipid homeostasis of L. vannamei. This disruption compelled L. vannamei to allocate additional energy toward sustaining basal physiological functions and consequently caused the accumulation of large amounts of reactive oxygen species (ROS) in the body, leading to apoptosis and subsequent tissue damage, and ultimately suppressed the immune system and impaired the health of L. vannamei. Our study elucidates the molecular mechanisms of CuPT-induced metabolic disruption and immunotoxicity in L. vannamei through integrated multi-omics analyses, providing new insights for ecological risk assessment of this emerging antifoulant. Full article

Liver, the center of substance metabolism, plays a vital role in the hibernation of mammals, a topic arousing increasing interest from researchers around the world. However, it remains unclear how the liver regulates energy metabolism during the hibernation of mammals. Metabolic disorders in the liver are closely associated with numerous diseases. In this research on chipmunks (Tamias sibiricus), we compared histological changes in the liver and energy source between the conditions for hibernation and room temperature, and subsequently conducted transcriptome sequencing analysis. The results demonstrate that lipid metabolism becomes a significant energy source during hibernation via the retinol signaling pathway and PPAR signaling pathway, thereby suggesting the importance of the liver in maintaining homeostasis when facing hypothermia. Furthermore, the result provides us with a novel perspective to obtain an insight into liver metabolic reprogramming and potential therapeutic strategies for metabolic disease in the liver. Full article

Background/Objectives: Generating real-world data on the efficacy of multidisciplinary care in cardiometabolic risk management is essential to ensure that guidelines are both applicable and effective, especially in public healthcare settings, where organizational structures may impede healthcare professionals’ agility. This study aimed to generate data on patient follow-up and cardiometabolic risk management during the early years of a public university family medicine group in Québec (Canada) that provides multidisciplinary care to adults with cardiometabolic conditions, in order to evaluate the implementation and effectiveness of its care model. Methods: This was a retrospective longitudinal study. Patients treated at the clinic from 31 January 2020 (clinic opening) to 8 May 2024 (n = 96) were invited to consent to the use of their medical data for research. Results: A total of 52 patients consented and were included in the study. Upon entry at the clinic, >90% of patients had anthropometry and blood pressure (BP) measured, but plasma glucose and lipids were assessed among 50% and 79% of patients, respectively. A total of 36 patients completed the personalized multidisciplinary care program. No evidence of associations between the total number of appointments or appointments with the registered dietitian specifically with changes in BMI, waist circumference, and BP was found. However, each pharmaceutical intervention was associated with a −0.51 cm (95%CI: −1.03, 0.02; p = 0.06) change in waist circumference and a −1.49 mm Hg (95%CI: −2.56, −0.43, p = 0.01) change in diastolic BP. Conclusions: These data highlight the challenges of implementing a research-oriented clinic within Québec’s public healthcare system. Full article

Cardiovascular disease remains the world’s leading cause of death, and even when patients reach guideline low-density lipoprotein cholesterol targets, a substantial “residual risk” persists, underscoring the need for more nuanced assessment and intervention. At the same time, rapid advances in high-resolution lipidomics, connected point-of-care diagnostics, and RNA- or gene-based lipid-modifying therapies are transforming what clinicians can measure, monitor, and treat. Integrating multimodal data through machine learning algorithms capable of handling high-dimensional datasets has the potential to improve cardiovascular risk prediction and re-stratification compared to traditional models. This narrative review therefore sets out to (i) trace how these emerging technologies expand our understanding of dyslipidemia beyond the traditional lipid panel, (ii) examine their potential to enable earlier, more personalized and durable cardiovascular risk reduction, and (iii) highlight the scientific, regulatory and ethical hurdles that must be cleared before such innovations can deliver widespread, equitable benefit. Full article

The virus-first theory presents a model in which viral lineages emerged before cells. This proposal aims to give the theory greater relevance by offering a plausible evolutionary framework that explains both (i) the origin of viruses from prebiotic chemistry and (ii) how viruses contributed to the emergence of cells. Here, we propose that viruses should be understood as a distinct class of ribonucleoprotein (RNP) systems, some of which evolved directly from the RNP-world. In our model, simple progenotes produced capsid-like particles through the evolution of a single gene encoding a self-assembling peptide. This allowed the formation of icosahedral shells around RNA genomes, as observed today in certain viral families whose capsids consist of ~60 identical subunits derived from a single gene product. These early capsids enabled mobility and protection, representing key intermediates toward biological complexity. Over time, some of those populations acquired additional peptides and evolved more elaborate architectures. Finally, the incorporation of lipid-binding domains in those capsid-like peptides allowed the formation of proteolipidic membranes akin to those found in modern cells. This model provides a gradualistic and logically coherent evolutionary path from the RNP-world to the emergence of cellular life, emphasizing the foundational role of viruses in early evolution. Full article

Background: Inclisiran is a novel lipid-lowering agent targeting PCSK9 via small interfering RNA (siRNA) technology. While clinical trials such as the ORION studies have demonstrated significant reductions in low-density lipoprotein cholesterol (c-LDL), real-world data (RWD) often differ due to variations in patient populations and clinical practices. Methods: This systematic review and meta-analysis adhered to PRISMA guidelines. A comprehensive search was conducted in MEDLINE for real-world studies evaluating inclisiran’s efficacy in reducing c-LDL. Articles meeting predefined inclusion criteria were assessed for quality and bias using RTI Item Bank. Data transformations were applied to harmonize median and IQR values to means and standard deviations for meta-analytic synthesis using RevMan 5.4. Results: A total of 3774 articles were identified, of which 7 studies comprising 1454 patients met the inclusion criteria. The meta-analysis revealed an average c-LDL reduction of 42.77% (95% CI: 37.42–48.12%). The subgroup analysis indicated greater reductions in patients receiving inclisiran alongside statins (45.67%; 95% CI: 36.64–54.71%) compared to monotherapy (37.53%; 95% CI: 29.91–45.15%). Discrepancies with clinical trials (e.g., 52% reduction in ORION studies) were attributed to baseline c-LDL differences and real-world adherence. Conclusions: Inclisiran demonstrates robust efficacy in real-world settings, achieving significant c-LDL reductions with a convenient dosing schedule. However, the observed discrepancies with clinical trials highlight the need for further RWD studies to bridge gaps in effectiveness and optimize therapeutic outcomes. Full article

Background: Oral semaglutide, a GLP1-receptor agonist (GLP1-RA), shows promise in efficacy and compliance, especially amid the global shortage of injectable GLP-1 RAs. Its short-term effectiveness remains unexplored. Objective: This real-world observational study assessed the short-term effectiveness of oral semaglutide after three months of therapy. Methods: Patients with type 2 diabetes from four Italian diabetes centers, who received an initial prescription of oral semaglutide, were reassessed after three months. Primary outcomes included glycated hemoglobin (HbA1c) and body weight reduction; secondary outcomes involved changes in lipid parameters and cardiovascular risk. Results: Among 167 participants (mean age 66.5 years, mostly obese, baseline HbA1c 8.4% ± 1.5), 83.2% received a 7 mg dose. After three months, HbA1c significantly declined (8.4% to 7.1%, −1.3%, p < 0.001), alongside body mass index (BMI) (30.9 kg/m² to 29.6 kg/m², p < 0.0001). The target HbA1c ≤ 7% was achieved by 54.5%, and 34.7% reached ≤6.5%. Patients losing >5% of their initial weight (30.5%) saw the largest HbA1c drop (−1.9%). Those with newly diagnosed diabetes or a duration < 5 years showed superior responses (p = 0.001), while no significant differences were found based on the timing of drug administration. Oral semaglutide replaced or supplemented prior therapies, allowing discontinuation of dipeptidyl peptidase 4 inhibitors (DPP4i), sulfonylureas, glinides, and acarbose, and deprescription of thiazolidinediones. A significant reduction in cardiovascular risk was observed (p = 0.04), together with a significant reduction in lipid parameters. Conclusions: Oral semaglutide showed significant short-term efficacy, reducing HbA1c, body weight, and cardiovascular risk in three months, making it a valuable therapeutic option. Full article

Rice is a fundamental food source for more than fifty percent of the world’s population, significantly contributing to human nutrition and food security. Like other cereal grains, rice is rich in starch, although it also contains protein, vitamins, and minerals. Regular consumption of white rice has been reported to be positively associated with the increased risk of type 2 diabetes in rice-consuming countries due to the high glycemic index (GI) of white rice. However, the nutritional value and health effects of rice differ markedly depending on the variety and are influenced by processing methods, cooking styles employed, and the presence of other food components/ingredients. Therefore, this review examines the chemical compositions, starch structures, and glycemic indices of different rice types and the impact of processing techniques and genetic mutation on starch’s structure, amylose content, and GI. The interactions between rice starch and other food components, such as proteins, lipids, dietary fibers, and polyphenols, and their impact on the digestibility and GI of rice starch are also discussed. The purpose of this comprehensive review is to elucidate the strategies that can improve the nutritional advantages of rice and mitigate health issues, such as obesity, diabetes, and inflammation, linked to the long-term consumption of rice. Full article

Background/Objectives: Liver disease is one of the most common medical problems in the world. The pharmacological correction of these pathologies includes the use of drugs with antioxidant and hepatoprotective action, among which there are natural and synthetic sulfur-containing compounds. However, many of these drugs have side effects, and their application does not always correspond to approaches in evidence-based medicine. Therefore, today the urgent problem is the search for new effective substances with high metabolitotropic properties and high safety criteria. The aim of this work was an in-depth study of the hepatoprotective and antioxidant action of a new investigational pteridine-containing “lead-compound” (DCTP) under conditions of experimental tetrachloromethane hepatitis in rats in comparison with the reference drug “Thiotriazoline”. Methods: The hepatoprotective effect of the compound was studied using a model of acute tetrachloromethane (CCl₄) hepatitis in adult male Wistar rats. The levels of biochemical liver damage markers were estimated with spectrophotometric methods. Histological and immunohistochemical methods were used for the determination of hepatocyte damage. The statistical processing of data was performed using the nonparametric Wilcoxon–Mann–Whitney method. Results: The results of the studies showed that DCTP was superior to the reference drug Thiotriazoline in terms of its effect on the levels of AST, DC, Schiff bases, and carbonylated proteins, which are markers of oxidative (Nrf2) and inflammatory (Lipocalin-2) stress, as well as its effect on animal survival. The results were confirmed by histological examination data, which showed regeneration of the hepatocyte membrane structure; a reduction in infiltrative, destructive, and inflammatory process in the liver; a reduction in the cytolytic process; stabilization; and an increase in the functional activity of the liver due to the administration of the study drug. The pharmacological effects of the studied compound (DCTP) are probably associated with its structural similarity to tetrahydrofolic acid, which is an integral component of oxidation–reduction processes and a participant in the biosynthesis of nitrogenous bases of nucleotides and amino acids. The obtained data show the antioxidant and hepatoprotective properties of the studied “lead-compound” from the pteridinethione group (DCTP). Conclusions: It was shown that the studied substance DCTP significantly reduces acute hepatotoxic effects caused by CCl₄, as evidenced by the decrease in the level of lipid peroxidation and prooxidant markers, the normalization of liver biochemical markers, the regeneration of the liver architecture, the limitation of inflammatory effects, the decrease in Nrf2 and Lipocalin-2 markers, and the induction of liver antioxidant enzymes. Full article

Background: Diabetes mellitus is a heterogeneous metabolic disorder that poses substantial challenges in the management of patients with diabetes. Emerging research underscores the potential of unsupervised cluster analysis as a promising methodological approach for unraveling the complex heterogeneity of diabetes mellitus. This systematic review evaluated the effectiveness of unsupervised cluster analysis in identifying diabetes phenotypes, elucidating the risks of diabetes-related complications, and distinguishing treatment responses. Methods: We searched MEDLINE Complete, PubMed, and Web of Science and reviewed forty-one relevant studies. Additionally, we conducted a cross-sectional study using K-means cluster analysis of real-world clinical data from 558 patients with diabetes. Results: A key finding was the consistent reproducibility of the five clusters across diverse populations, encompassing various patient origins and ethnic backgrounds. MOD and MARD were the most prevalent clusters, while SAID was the least prevalent. Subgroup analysis stratified by ethnic group indicated a higher prevalence of SIDD among individuals of Asian descent than among other ethnic groups. These clusters shared similar phenotypic traits and risk profiles for complications, with some variations in their distribution and key clinical variables. Notably, the SIRD subtype was associated with a wide spectrum of kidney-related clinical presentations. Alternative clustering techniques may reveal additional clinically relevant diabetes subtypes. Our cross-sectional study identified five subgroups, each with distinct profiles of glycemic control, lipid metabolism, blood pressure, and renal function. Conclusions: Overall, the results suggest that unsupervised cluster analysis holds promise for revealing clinically meaningful subgroups with distinct characteristics, complication risks, and treatment responses that may remain undetected using conventional approaches. Full article

Pineapple (Ananas comosus L.), cashew (Anacardium occidentale L.) and mango (Mangifera indica L.) are among the most cultivated plants in tropical and subtropical regions due to the high demand around the world. Following the harvesting and processing of pineapple, cashew and mango fruits, a huge amount of waste is generated, which is generally discarded into the environment, contributing to global pollution and water contamination. This study aims to propose alternative feeds for pigs by characterizing cashew, pineapple and mango fruit by-products through an in vitro two-step (gastro-intestinal and caecum) study to provide feeds not competing with humans and promoting eco-sustainable livestock. Ten by-products [i.e., pineapple peel and pomace; cashew nut testa, cashew (var. yellow) whole fruit and pomace; cashew (var. red) whole fruit and pomace; mango peel, kernel and testa] were sampled in Benin. The samples involved chemical analysis and an in vitro two-step digestion method (enzymatic + microbial digestibility). The results report a low dry matter (DM) content specifically in the pomace, peel and whole apple (13.0–27.2%), while higher lipids were observed for cashew nut testa and mango kernel (26.4 and 11.2% DM). The investigated by-products fall within the interval of referenced feeds for structural carbohydrates (NDF: 7.6–47.1% DM) and protein (6.21–51.2% DM), except mango by-products with a low content of protein (2.51–4.69% DM). The total dry matter digestibility, short-chain fatty acid and gas production were low for cashew by-products and stopped after 48 h of incubation. Pineapple pomace, cashew whole apple, pomace and testa can be considered as feedstuff in fattening pigs, presenting characteristics partly similar to beet pulp. Indeed, mango peel and kernel should be combined with a protein feed source to feed pigs. Presently, fruit by-products, such as those from cashew, pineapple and mango, are thrown into the environment, contributing to global warming and water pollution. These problems would be reduced by recycling these wastes in other fields, such as pig nutrition, creating a circular economy to provide feeds promoting eco-sustainable livestock. Indeed, in vivo studies are needed before proposing these by-products for pig diets. Full article

Background: The global burden of obesity and type 2 diabetes mellitus is a significant contributor to mortality and disability in the modern world. In this regard, the modification of adipocyte metabolism has been identified as a promising approach to develop new genetic and cellular engineering therapeutics. In this study, we activate the expression of creatine kinase B (CKB), a key enzyme of a non-canonical futile cycle and the regulator of energy storage, to promote catabolic processes in mature adipocytes. Methods: The protein-coding sequence of CKB was amplified by PCR from Mus musculus brain mRNA. Lentiviral transduction was used to transfer the CKB sequence into mature adipocytes. Adipocyte metabolism was analyzed by radioisotope monitoring of labeled [3H]-2-deoxyglucose and [14C]-glucose. Confocal microscopy was applied to estimate lipid droplets morphology (BODIPY493/503 dye), mitochondrial membrane potential (JC-1 dye), and thermogenesis (ERthermAC dye). Results: After lentiviral delivery of the CKB-coding sequence, CKB mRNA level increased 75-fold and protein expression fivefold. CKB overexpression does not cause significant changes in lipid droplet morphology. Despite this, enhanced glucose uptake and reduced lipid synthesis under adrenergic stimulation are detected during CKB overexpression. CKB causes an increase in mitochondrial potential with no effect on thermogenesis in adipocytes. Conclusions: In this study, we have shown that CKB overexpression in mature adipocytes allows us to obtain adipocytes with high glucose uptake, potency of ATP synthesis, and suppressed lipogenesis. These genetically modified cells may potentially exhibit a favorable metabolic effect in the context of excessive nutrient utilization. Full article